T-wave alternans train spotter

ABSTRACT

A method and system for detecting T-wave alternans for use in an implanted medical device uses wave transformation of QT intervals to obtain a reliable measure of TWA. In one embodiment, an array provides alternating sign multiplication factors which are applied respectively to n consecutive QT values. Each successive QT value is high pass filtered and moved sequentially through a queue so that each cycle each of the n QT values is multiplied by one of the factors; the products are summed and made absolute to provide an alternans match value. The alternans match is compared with a noise threshold signal, and alternans is declared when the match exceeds the threshold by a predetermined amount. The array is programmable and can be varied, providing a high degree of flexibility to optimize the test for the patient.

RELATED APPLICATION

[0001] The present invention claims priority and other benefits fromU.S. Provisional Patent Application Serial No. 60/439,459, filed Jan.13, 2003, entitled “T-WAVE ALTERNANS TRAIN SPOTTER”, incorporated hereinby reference in its entirety.

FIELD OF THE INVENTION

[0002] This invention relates to cardiac devices and methods of usingsuch devices and, more particularly, devices and methods for detectingT-wave alternans in a cardiac patient.

BACKGROUND OF THE INVENTION

[0003] It has become well known that T-wave alternans has predictivevalue for arrhythmic events such as tachyarrhythmias. T-wave alternanshas been determined to be an indicator of various forms of disorderedventricular repolarization, including disorders found in patients withcardiomyopathy, mild to moderate heart failure, and congestive heartfailure. The following literature references deal with the subject ofT-wave alternans as a predictor: Klingenheben T, Siedow A, Credner S C,Gronefeld, et al., T-Wave Alternans in microwave frequency as a newindicator of disordered ventricular repolarization: pathophysiology,methodology, clinical results, Z Kardiol, 1999, Dec, 88 (12), 974-81;Klingenheben T, Zabel M, D'Agostino R B, Cohen R J et al., Predictivevalue of T-Wave Alternans for arrhythmic events in patients withcongestive heart failure, Lancet, 2000, Aug 19; 356(9230): 651-2; andHennersdorf M G, Perings C, Niebch V, Vester E G, et. al., T-WaveAlternans as a risk predictor in patients with cardiomyopathy andmild-to-moderate heart failure, Pacing Clin Electrophysiol 2000 Sep;23(9); 1386-91.

[0004] T-wave alternans (TWA) may be caused by changes in ion exchangeduring repolarization. If there is a change in the repolarizationmechanism on one beat, the heart attempts to readjust on the followingbeat. This is manifested as an alternating change in the actionpotential. In the surface ECG this is seen primarily as an amplitudechange. For an implanted medical device such as a cardiac pacemaker, theintracardiac electrogram (iecg) also shows a change in timing. Thus, theterm T-wave as used herein may refer to a portion of the ventricularQRS-T-wave complex that includes the T-wave and the QRS-T segment. Thealternating feature of TWA can be detected by examination, for example,of the QT interval, T-wave width, T-wave morphology, etc. Whatever thedesignated portion of the iecg, T-wave alternans refers to analternating pattern of the wave that can be designated “A-B-A-B-A . . .” where A represents every other cycle and B represents every otheralternate cycle. As discussed in the literature, when such analternating pattern appears, the different rates or forms ofrepolarization of the ventricular cells are statistically associatedwith a variety abnormal cardiac conditions. Further, the alternatingrepolarization pattern can lead to increased instability and consequentcardiac arrhythmias. Thus, T-wave alternans is recognized as anindicator of risk for ventricular arrhythmia and even sudden cardiacdeath.

[0005] The prior art discloses several different methods and techniquesfor detecting T-wave alternans. TWA can be measured non-invasively byexercise-inducing an elevated heart rate in the patient and thenmeasuring the surface ECG with special electrodes and computer analysis.Moreover, it has been disclosed that measurement of the TWA through theIECG obtained by an implanted medical device provides the capability ofobtaining improved waveform data and analysis for detection of TWA. SeeU.S. patent application Ser. No. 09/558,871, filed Apr. 28, 2000,“Implantable Medical Device and Method Using Integrated T-Wave AlternansAnalyzer”, Morris et al. This patent is incorporated herein by referencein its entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Various aspects and features of the present invention will bereadily appreciated as the same becomes better understood by referenceto the following detailed description when considered in connection withthe accompanying drawings, in which like reference numerals designatelike parts throughout the figures thereof and wherein:

[0007]FIG. 1 is a simplified schematic view of one embodiment of animplantable medical device that can be employed in the presentinvention.

[0008]FIG. 2 is a graphic representation of an implantable medicaldevice interconnected with a human or mammalian heart, illustrating thedevice connecter portion and the leads between the device and the heart.

[0009]FIG. 3 is a functional schematic diagram showing the primaryconstituent components of an implantable medical device in accordancewith an embodiment of this invention.

[0010]FIG. 4 is a graphic representation of an embodiment of thisinvention showing an implantable PCD device interconnected with theheart, the system of this embodiment providing pacing, cardioversion anddefibrillation.

[0011]FIG. 5 is a functional schematic diagram of an implantable PCDembodiment in accord with this invention.

[0012]FIG. 6 is a schematic wavelet transformation diagram fordetermining T-Wave ALternans in accordance with this invention.

[0013]FIG. 7 is a flow diagram illustrating the steps taken in carryingout the wavelet transformation of FIG. 6.

[0014]FIG. 8 shows a comparison of QT interval data and alternans matchdata, representing the practice of this invention.

[0015]FIG. 9 is a flow diagram showing the primary steps for determiningTWA in accord with this invention.

[0016]FIG. 10 is a flow diagram showing steps taken in carrying out theT-wave alternans test and in adapting the pattern array in accord withthis invention.

DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention provides a system and method fordetermining TWA in a patient, the system and method constituting animprovement over the prior art that enables a more accurate detection ofTWA and more flexibility in optimizing TWA detection for the patientunder examination.

[0018] In an embodiment of the present invention, an adaptabletransformation program is utilized for applying an alternating signarray to a series of consecutive T-wave signals. As used in theSpecification and Claims that follow, T-wave comprises not only theT-wave portion of the ventricular IECG but also the S-T segment or theQ-T interval. In the an embodiment of the invention, QT intervals aresensed each cycle, and the invention operates cyclically to provide anindication of whether or not T-wave alternans has been detected.

[0019] In an embodiment of the invention, a transformation array is inthe form A-B-A, A-B-A-B, A-B-A-B-A, etc. where A is a positive factorand a B is a negative factor. Consecutive values of QT (or other portionof the sensed ventricular wave) are stored in a queue, multipliedrespectively by the pattern factors, and then summed. The pattern mayhave an odd number of factors or an even number of factors. The patternarray may be programmable or automatically selected from a plurality ofdifferent arrays, thereby providing the user with the ability tooptimize the pattern for the individual patient. After each factor ofthe array is multiplied by the corresponding respective QT interval fromthe series of QT intervals being examined, the products are summed andthen preferably squared to get an absolute value. This absolute value,referred to as the alternans match, is compared to a noise thresholdthat is representative of the noise level in the QT sensor. When thealternans match exceeds threshold, alternans is deemed to have beendetermined.

[0020] In another embodiment of the invention the QT signals are highpass filtered before undergoing transformation, removing the steadystate value of each AT interval so that the transformation is done onplus and minus differential values. The filtering function may beundertaken by hardware such as is available from a DSP chip.Alternately, the high pass filter function may be incorporated into thepattern, so that the transformation operation on each series of QTintervals incorporates the high pass filtering step. This makesimplementation of the method simpler and requires less computingresources, which is of course advantageous for an implanted device.

[0021] In the system of this invention the result of each T-wavealternans analysis is suitably stored in memory for later interrogationand retrieval. Further, for each T-wave alternans test, the pattern used(e.g., the number of factors and the value of each of the factors of thepattern) can be stored, so that a determination can be made as to theoptimum pattern for the patient.

[0022]FIG. 1 is a simplified schematic view of one embodiment ofimplantable medical device (“IMD”) 10 of the present invention. IMD 10shown in FIG. 1 is a pacemaker comprising at least one of pacing andsensing leads 16 and 18 attached to hermetically sealed enclosure 14 andimplanted near human or mammalian heart 8. Pacing and sensing leads 16and 18 sense electrical signals attendant to the depolarization andre-polarization of the heart 8, and further provide pacing pulses forcausing depolarization of cardiac tissue in the vicinity of the distalends thereof. Leads 16 and 18 may have unipolar or bipolar electrodesdisposed thereon, as is well known in the art. Examples of IMD 10include implantable cardiac pacemakers disclosed in U.S. Pat. No.5,158,078 to Bennett et al., U.S. Pat. No. 5,312,453 to Shelton et al.or U.S. Pat. No. 5,144,949 to Olson, all hereby incorporated byreference herein, each in its respective entirety.

[0023]FIG. 2 shows connector module 12 and hermetically sealed enclosure14 of IMD 10 located in and near human or mammalian heart 8. Atrial andventricular pacing leads 16 and 18 extend from connector header module12 to the right atrium and ventricle, respectively, of heart 8. Atrialelectrodes 20 and 21 disposed at the distal end of atrial pacing lead 16are located in the right atrium. Ventricular electrodes 28 and 29 at thedistal end of ventricular pacing lead 18 are located in the rightventricle.

[0024]FIG. 3 shows a block diagram illustrating the constituentcomponents of IMD 10 in accordance with one embodiment of the presentinvention, where IMD 10 is pacemaker having a microprocessor-basedarchitecture. IMD 10 is shown as including activity sensor oraccelerometer 11, which is preferably a piezoceramic accelerometerbonded to a hybrid circuit located inside enclosure 14. Activity sensor11 typically (although not necessarily) provides a sensor output thatvaries as a function of a measured parameter relating to a patient'smetabolic requirements. For the sake of convenience, IMD 10 in FIG. 3 isshown with lead 18 only connected thereto; similar circuitry andconnections not explicitly shown in FIG. 3 apply to lead 16.

[0025] IMD 10 in FIG. 3 is most preferably programmable by means of anexternal programming unit (not shown in the Figures). One suchprogrammer is the commercially available Medtronic Model 9790programmer, which is microprocessor-based and provides a series ofencoded signals to IMD 10, typically through a programming head whichtransmits or telemeters radio-frequency (RF) encoded signals to IMD 10.Such a telemetry system is described in U.S. Pat. No. 5,312,453 toWyborny et al., hereby incorporated by reference herein in its entirety.The programming methodology disclosed in Wyborny et al.'s '453 patent isidentified herein for illustrative purposes only. Any of a number ofsuitable programming and telemetry methodologies known in the art may beemployed so long as the desired information is transmitted to and fromthe pacemaker.

[0026] As shown in FIG. 3, lead 18 is coupled to node 50 in IMD 10through input capacitor 52. Activity sensor or accelerometer 11 is mostpreferably attached to a hybrid circuit located inside hermeticallysealed enclosure 14 of IMD 10. The output signal provided by activitysensor 11 is coupled to input/output circuit 54. Input/output circuit 54contains analog circuits for interfacing to heart 8, activity sensor 11,antenna 56 and circuits for the application of stimulating pulses toheart 8. The rate of heart 8 is controlled by software-implementedalgorithms stored in microcomputer circuit 58.

[0027] Microcomputer circuit 58 preferably comprises on-board circuit 60and off-board circuit 62. Circuit 58 may correspond to a microcomputercircuit disclosed in U.S. Pat. No. 5,312,453 to Shelton et al., herebyincorporated by reference herein in its entirety. On-board circuit 60preferably includes microprocessor 64, system clock circuit 66 andon-board RAM 68 and ROM 70. Off-board circuit 62 preferably comprises aRAM/ROM unit. On-board circuit 60 and off-board circuit 62 are eachcoupled by data communication bus 72 to digital controller/timer circuit74. Microcomputer circuit 58 may comprise a custom integrated circuitdevice augmented by standard RAM/ROM components.

[0028] Electrical components shown in FIG. 3 are powered by anappropriate implantable battery power source 76 in accordance withcommon practice in the art. For the sake of clarity, the coupling ofbattery power to the various components of IMD 10 is not shown in theFigures. Antenna 56 is connected to input/output circuit 54 to permituplink/downlink telemetry through RF transmitter and receiver telemetryunit 78. By way of example, telemetry unit 78 may correspond to thatdisclosed in U.S. Pat. No. 4,566,063 issued to Thompson et al., herebyincorporated by reference herein in its entirety, or to that disclosedin the above-referenced '453 patent to Wyborny et al. According to anembodiment of the invention, the particular programming and telemetryscheme are selected to permit the entry and storage of cardiacrate-response parameters. The specific embodiments of antenna 56,input/output circuit 54 and telemetry unit 78 presented herein are shownfor illustrative purposes only, and are not intended to limit the scopeof the present invention.

[0029] Continuing to refer to FIG. 3, V_(REF) and Bias circuit 82 mostpreferably generates stable voltage reference and bias currents foranalog circuits included in input/output circuit 54. Analog-to-digitalconverter (ADC) and multiplexer unit 84 digitizes analog signals andvoltages to provide “real-time” telemetry intracardiac signals andbattery end-of-life (EOL) replacement functions. Operating commands forcontrolling the timing of IMD 10 are coupled by data bus 72 to digitalcontroller/timer circuit 74, where digital timers and counters establishthe overall escape interval of the IMD 10 as well as various refractory,blanking and other timing windows for controlling the operation ofperipheral components disposed within input/output circuit 54.

[0030] Digital controller/timer circuit 74 is preferably coupled tosensing circuitry, including sense amplifier 88, peak sense andthreshold measurement unit 90 and comparator/threshold detector 92.Circuit 74 is further preferably coupled to electrogram (EGM) amplifier94 for receiving amplified and processed signals sensed by lead 18.Sense amplifier 88 amplifies sensed electrical cardiac signals andprovides an amplified signal to peak sense and threshold measurementcircuitry 90, which in turn provides an indication of peak sensedvoltages and measured sense amplifier threshold voltages on multipleconductor signal path 67 to digital controller/timer circuit 74. Anamplified sense amplifier signal is then provided tocomparator/threshold detector 92. By way of example, sense amplifier 88may correspond to that disclosed in U.S. Pat. No. 4,379,459 to Stein,hereby incorporated by reference herein in its entirety. The functionsperformed by elements 88,90,92 may alternately be performed by an inputDSP chip as shown at 100; the DSP chip may also perform other functionssuch as high pass filtering and array transformation, as discussed belowin detail.

[0031] The electrogram signal provided by EGM amplifier 94 is employedwhen IMD 10 is being interrogated by an external programmer to transmita representation of a cardiac analog electrogram. See, for example, U.S.Pat. No. 4,556,063 to Thompson et al., hereby incorporated by referenceherein in its entirety. Output pulse generator 96 provides pacingstimuli to patient's heart 8 through coupling capacitor 98 in responseto a pacing trigger signal provided by digital controller/timer circuit74 each time the escape interval times out, an externally transmittedpacing command is received or in response to other stored commands as iswell known in the pacing art. By way of example, output amplifier 96 maycorrespond generally to an output amplifier disclosed in U.S. Pat. No.4,476,868 to Thompson, hereby incorporated by reference herein in itsentirety.

[0032] The specific embodiments of input amplifier 88, output amplifier96 and EGM amplifier 94 identified herein are presented for illustrativepurposes only, and are not intended to be limiting in respect of thescope of the present invention. The specific embodiments of suchcircuits may not be critical to practicing some embodiments of thepresent invention so long as they provide means for generating astimulating pulse and are capable of providing signals indicative ofnatural or stimulated contractions of heart 8.

[0033] In some embodiments of the present invention, IMD 10 may operatein various non-rate-responsive modes, including, but not limited to,DDD, DDI, VVI, VOO and VVT modes. In other embodiments of the presentinvention, IMD 10 may operate in various rate-responsive, including, butnot limited to, DDDR, DDIR, VVIR, VOOR and VVTR modes. Some embodimentsof the present invention are capable of operating in bothnon-rate-responsive and rate responsive modes. Moreover, in variousembodiments of the present invention IMD 10 may be programmablyconfigured to operate so that it varies the rate at which it deliversstimulating pulses to heart 8 only in response to one or more selectedsensor outputs being generated. Numerous pacemaker features andfunctions not explicitly mentioned herein may be incorporated into IMD10 while remaining within the scope of the present invention.

[0034] The present invention is not limited in scope to single-sensor ordual-sensor pacemakers, and is not limited to IMD's comprising activityor pressure sensors only. Nor is the present invention limited in scopeto single-chamber pacemakers, single-chamber leads for pacemakers orsingle-sensor or dual-sensor leads for pacemakers. Thus, variousembodiments of the present invention may be practiced in conjunctionwith more than two leads or with multiple-chamber pacemakers, forexample. At least some embodiments of the present invention may beapplied equally well in the contexts of single-, dual-, triple- orquadruple-chamber pacemakers or other types of IMD's. See, for example,U.S. Pat. No. 5,800,465 to Thompson et al., hereby incorporated byreference herein in its entirety, as are all U.S. patents referencedtherein.

[0035] IMD 10 may also be a pacemaker-cardioverter-defibrillator (“PCD”)corresponding to any of numerous commercially available implantablePCD's. Various embodiments of the present invention may be practiced inconjunction with PCD's such as those disclosed in U.S. Pat. No.5,545,186 to Olson et al., U.S. Pat. No. 5,354,316 to Keimel, U.S. Pat.No. 5,314,430 to Bardy, U.S. Pat. No. 5,131,388 to Pless and U.S. Pat.No. 4,821,723 to Baker et al., all hereby incorporated by referenceherein, each in its respective entirety.

[0036]FIGS. 4 and 5 illustrate one embodiment of IMD 10 and acorresponding lead set of the present invention, where IMD 10 is a PCD.In FIG. 4, the ventricular lead takes the form of leads disclosed inU.S. Pat. Nos. 5,099,838 and 5,314,430 to Bardy, and includes anelongated insulative lead body 1 carrying three concentric coiledconductors separated from one another by tubular insulative sheaths.Located adjacent the distal end of lead 1 are ring electrode 2,extendable helix electrode 3 mounted retractably within insulativeelectrode head 4 and elongated coil electrode 5. Each of the electrodesis coupled to one of the coiled conductors within lead body 1.Electrodes 2 and 3 are employed for cardiac pacing and for sensingventricular depolarizations. At the proximal end of the lead isbifurcated connector 6 which carries three electrical connectors, eachcoupled to one of the coiled conductors. Defibrillation electrode 5 maybe fabricated from platinum, platinum alloy or other materials known tobe usable in implantable defibrillation electrodes and may be about 5 cmin length.

[0037] The atrial/SVC lead shown in FIG. 4 includes elongated insulativelead body 7 carrying three concentric coiled conductors separated fromone another by tubular insulative sheaths corresponding to the structureof the ventricular lead. Located adjacent the J-shaped distal end of thelead are ring electrode 9 and extendable helix electrode 13 mountedretractably within an insulative electrode head 15. Each of theelectrodes is coupled to one of the coiled conductors within lead body7. Electrodes 13 and 9 are employed for atrial pacing and for sensingatrial depolarizations. Elongated coil electrode 19 is provided proximalto electrode 9 and coupled to the third conductor within lead body 7.Electrode 19 preferably is 10 cm in length or greater and is configuredto extend from the SVC toward the tricuspid valve. In one embodiment ofthe present invention, approximately 5 cm of the right atrium/SVCelectrode is located in the right atrium with the remaining 5 cm locatedin the SVC. At the proximal end of the lead is bifurcated connector 17carrying three electrical connectors, each coupled to one of the coiledconductors.

[0038] The coronary sinus lead shown in FIG. 4 assumes the form of acoronary sinus lead disclosed in the above cited '838 patent issued toBardy, and includes elongated insulative lead body 41 carrying onecoiled conductor coupled to an elongated coiled defibrillation electrode21. Electrode 21, illustrated in broken outline in FIG. 4, is locatedwithin the coronary sinus and great vein of the heart. At the proximalend of the lead is connector plug 23 carrying an electrical connectorcoupled to the coiled conductor. The coronary sinus/great vein electrode41 may be about 5 cm in length.

[0039] Implantable PCD 10 is shown in FIG. 4 in combination with leads1, 7 and 41, and lead connector assemblies 23, 17 and 6 inserted intoconnector block 12. Optionally, insulation of the outward facing portionof housing 14 of PCD 10 may be provided using a plastic coating such asparylene or silicone rubber, as is employed in some unipolar cardiacpacemakers. The outward facing portion, however, may be left uninsulatedor some other division between insulated and uninsulated portions may beemployed. The uninsulated portion of housing 14 serves as a subcutaneousdefibrillation electrode to defibrillate either the atria or ventricles.Lead configurations other that those shown in FIG. 4 may be practiced inconjunction with the present invention, such as those shown in U.S. Pat.No. 5,690,686 to Min et al., hereby incorporated by reference herein inits entirety.

[0040]FIG. 5 is a functional schematic diagram of one embodiment ofimplantable PCD 10 of the present invention. This diagram should betaken as exemplary of the type of device in which various embodiments ofthe present invention may be embodied, and not as limiting, as it isbelieved that the invention may be practiced in a wide variety of deviceimplementations, including cardioverter and defibrillators which do notprovide anti-tachycardia pacing therapies.

[0041] IMD 10 is provided with an electrode system. If the electrodeconfiguration of FIG. 4 is employed, the correspondence to theillustrated electrodes is as follows. Electrode 25 in FIG. 5 includesthe uninsulated portion of the housing of PCD 10. Electrodes 25, 15, 21and 5 are coupled to high voltage output circuit 27, which includes highvoltage switches controlled by CV/defib control logic 29 via control bus31. Switches disposed within circuit 27 determine which electrodes areemployed and which electrodes are coupled to the positive and negativeterminals of the capacitor bank (which includes capacitors 33 and 35)during delivery of defibrillation pulses.

[0042] Electrodes 2 and 3 are located on or in the ventricle and arecoupled to the R-wave amplifier 37, which preferably takes the form ofan automatic gain controlled amplifier providing an adjustable sensingthreshold as a function of the measured R-wave amplitude. A signal isgenerated on R-out line 39 whenever the signal sensed between electrodes2 and 3 exceeds the present sensing threshold.

[0043] Electrodes 9 and 13 are located on or in the atrium and arecoupled to the P-wave amplifier 43, which preferably also takes the formof an automatic gain controlled amplifier providing an adjustablesensing threshold as a function of the measured P-wave amplitude. Asignal is generated on P-out line 45 whenever the signal sensed betweenelectrodes 9 and 13 exceeds the present sensing threshold. The generaloperation of R-wave and P-wave amplifiers 37 and 43 may correspond tothat disclosed in U.S. Pat. No. 5,117,824, by Keimel et al., issued Jun.2, 1992, for “An Apparatus for Monitoring Electrical PhysiologicSignals”, hereby incorporated by reference herein in its entirety.

[0044] Switch matrix 47 is used to select which of the availableelectrodes are coupled to wide band (0.5-200 Hz) amplifier 49 for use indigital signal analysis. Selection of electrodes is controlled by themicroprocessor 51 via data/address bus 53, which selections may bevaried as desired. Signals from the electrodes selected for coupling tobandpass amplifier 49 are provided to multiplexer 55, and thereafterconverted to multi-bit digital signals by A/D converter 57, for storagein random access memory 59 under control of direct memory access circuit61. Microprocessor 51 may employ digital signal analysis techniques tocharacterize the digitized signals stored in random access memory 59 torecognize and classify the patient's heart rhythm employing any of thenumerous signal processing methodologies known to the art.

[0045] The remainder of the circuitry is dedicated to the provision ofcardiac pacing, cardioversion and defibrillation therapies, and, forpurposes of the present invention may correspond to circuitry known tothose skilled in the art. The following exemplary apparatus is disclosedfor accomplishing pacing, cardioversion and defibrillation functions.Pacer timing/control circuitry 63 preferably includes programmabledigital counters which control the basic time intervals associated withDDD, VVI, DVI, VDD, AAI, DDI and other modes of single and dual chamberpacing well known to the art. Circuitry 63 also preferably controlsescape intervals associated with anti-tachyarrhythmia pacing in both theatrium and the ventricle, employing any anti-tachyarrhythmia pacingtherapies known to the art.

[0046] Intervals defined by pacing circuitry 63 include atrial andventricular pacing escape intervals, the refractory periods during whichsensed P-waves and R-waves are ineffective to restart timing of theescape intervals and the pulse widths of the pacing pulses. Thedurations of these intervals are determined by microprocessor 51, inresponse to stored data in memory 59 and are communicated to pacingcircuitry 63 via address/data bus 53. Pacer circuitry 63 also determinesthe amplitude of the cardiac pacing pulses under control ofmicroprocessor 51.

[0047] During pacing, escape interval counters within pacertiming/control circuitry 63 are reset upon sensing of R-waves andP-waves as indicated by a signals on lines 39 and 45, and in accordancewith the selected mode of pacing on time-out trigger generation ofpacing pulses by pacer output circuitry 65 and 67, which are coupled toelectrodes 9, 13, 2 and 3. Escape interval counters are also reset ongeneration of pacing pulses and thereby control the basic timing ofcardiac pacing functions, including anti-tachyarrhythmia pacing. Thedurations of the intervals defined by escape interval timers aredetermined by microprocessor 51 via data/address bus 53. The value ofthe count present in the escape interval counters when reset by sensedR-waves and P-waves may be used to measure the durations of R-Rintervals, P-P intervals, P-R intervals and R-P intervals, whichmeasurements are stored in memory 59 and used to detect the presence oftachyarrhythmias.

[0048] Microprocessor 51 most preferably operates as an interrupt drivendevice, and is responsive to interrupts from pacer timing/controlcircuitry 63 corresponding to the occurrence sensed P-waves and R-wavesand corresponding to the generation of cardiac pacing pulses. Thoseinterrupts are provided via data/address bus 53. Any necessarymathematical calculations to be performed by microprocessor 51 and anyupdating of the values or intervals controlled by pacer timing/controlcircuitry 63 take place following such interrupts.

[0049] Detection of atrial or ventricular tachyarrhythmias, as employedin the present invention, may correspond to tachyarrhythmia detectionalgorithms known in the art. For example, the presence of an atrial orventricular tachyarrhythmia may be confirmed by detecting a sustainedseries of short R-R or P-P intervals of an average rate indicative oftachyarrhythmia or an unbroken series of short R-R or P-P intervals. Thesuddenness of onset of the detected high rates, the stability of thehigh rates, and a number of other factors known in the art may also bemeasured at this time. Appropriate ventricular tachyarrhythmia detectionmethodologies measuring such factors are described in U.S. Pat. No.4,726,380 issued to Vollmann, U.S. Pat. No. 4,880,005 issued to Pless etal. and U.S. Pat. No. 4,830,006 issued to Haluska et al., allincorporated by reference herein, each in its respective entirety. Anadditional set of tachycardia recognition methodologies is disclosed inthe article “Onset and Stability for Ventricular TachyarrhythmiaDetection in an Implantable Pacer-Cardioverter-Defibrillator” by Olsonet al., published in Computers in Cardiology, Oct. 7-10, 1986, IEEEComputer Society Press, pages 167-170, also incorporated by referenceherein in its entirety. Atrial fibrillation detection methodologies aredisclosed in Published PCT Application Ser. No. US92/02829, PublicationNo. WO92/18198, by Adams et al., and in the article “AutomaticTachycardia Recognition”, by Arzbaecher et al., published in PACE,May-June, 1984, pp. 541-547, both of which are incorporated by referenceherein in their entireties.

[0050] In the event an atrial or ventricular tachyarrhythmia is detectedand an anti-tachyarrhythmia pacing regimen is desired, appropriatetiming intervals for controlling generation of anti-tachyarrhythmiapacing therapies are loaded from microprocessor 51 into the pacer timingand control circuitry 63, to control the operation of the escapeinterval counters therein and to define refractory periods during whichdetection of R-waves and P-waves is ineffective to restart the escapeinterval counters.

[0051] Alternatively, circuitry for controlling the timing andgeneration of anti-tachycardia pacing pulses as described in U.S. Pat.No. 4,577,633, issued to Berkovits et al. on Mar. 25, 1986, U.S. Pat.No. 4,880,005, issued to Pless et al. on Nov. 14, 1989, U.S. Pat. No.4,726,380, issued to Vollmann et al. on Feb. 23, 1988 and U.S. Pat. No.4,587,970, issued to Holley et al. on May 13, 1986, all of which areincorporated herein by reference in their entireties, may also beemployed.

[0052] In the event that generation of a cardioversion or defibrillationpulse is required, microprocessor 51 may employ an escape intervalcounter to control timing of such cardioversion and defibrillationpulses, as well as associated refractory periods. In response to thedetection of atrial or ventricular fibrillation or tachyarrhythmiarequiring a cardioversion pulse, microprocessor 51 activatescardioversion/defibrillation control circuitry 29, which initiatescharging of the high voltage capacitors 33 and 35 via charging circuit69, under the control of high voltage charging control line 71. Thevoltage on the high voltage capacitors is monitored via VCAP line 73,which is passed through multiplexer 55 and in response to reaching apredetermined value set by microprocessor 51, results in generation of alogic signal on Cap Full (CF) line 77 to terminate charging. Thereafter,timing of the delivery of the defibrillation or cardioversion pulse iscontrolled by pacer timing/control circuitry 63. Following delivery ofthe fibrillation or tachycardia therapy microprocessor 51 returns thedevice to a cardiac pacing mode and awaits the next successive interruptdue to pacing or the occurrence of a sensed atrial or ventriculardepolarization.

[0053] Several embodiments of appropriate systems for the delivery andsynchronization of ventricular cardioversion and defibrillation pulsesand for controlling the timing functions related to them are disclosedin U.S. Pat. No. 5,188,105 to Keimel, U.S. Pat. No. 5,269,298 to Adamset al. and U.S. Pat. No. 4,316,472 to Mirowski et al., herebyincorporated by reference herein, each in its respective entirety. Anyknown cardioversion or defibrillation pulse control circuitry isbelieved to be usable in conjunction with various embodiments of thepresent invention, however. For example, circuitry controlling thetiming and generation of cardioversion and defibrillation pulses such asthat disclosed in U.S. Pat. No. 4,384,585 to Zipes, U.S. Pat. No.4,949,719 to Pless et al., or U.S. Pat. No. 4,375,817 to Engle et al.,all hereby incorporated by reference herein in their entireties, mayalso be employed.

[0054] Continuing to refer to FIG. 5, delivery of cardioversion ordefibrillation pulses is accomplished by output circuit 27 under thecontrol of control circuitry 29 via control bus 31. Output circuit 27determines whether a monophasic or biphasic pulse is delivered, thepolarity of the electrodes and which electrodes are involved in deliveryof the pulse. Output circuit 27 also includes high voltage switcheswhich control whether electrodes are coupled together during delivery ofthe pulse. Alternatively, electrodes intended to be coupled togetherduring the pulse may simply be permanently coupled to one another,either exterior to or interior of the device housing, and polarity maysimilarly be pre-set, as in current implantable defibrillators. Anexample of output circuitry for delivery of biphasic pulse regimens tomultiple electrode systems may be found in the above cited patent issuedto Mehra and in U.S. Pat. No. 4,727,877, hereby incorporated byreference herein in its entirety.

[0055] An example of circuitry which may be used to control delivery ofmonophasic pulses is disclosed in U.S. Pat. No. 5,163,427 to Keimel,also incorporated by reference herein in its entirety. Output controlcircuitry similar to that disclosed in U.S. Pat. No. 4,953,551 to Mehraet al. or U.S. Pat. No. 4,800,883 to Winstrom, both incorporated byreference herein in their entireties, may also be used in conjunctionwith various embodiments of the present invention to deliver biphasicpulses.

[0056] Alternatively, IMD 10 may be an implantable nerve stimulator ormuscle stimulator such as that disclosed in U.S. Pat. No. 5,199,428 toObel et al., U.S. Pat. No. 5,207,218 to Carpentier et al. or U.S. Pat.No. 5,330,507 to Schwartz, or an implantable monitoring device such asthat disclosed in U.S. Pat. No. 5,331,966 issued to Bennet et al., allof which are hereby incorporated by reference herein, each in itsrespective entirety. The present invention is believed to find wideapplication to any form of implantable electrical device for use inconjunction with electrical leads.

[0057]FIG. 6 is a schematic diagram of the pattern array transformationaccording to an embodiment of this invention. The illustrated steps canbe executed by software in the microprocessor, as illustrated in FIG. 7,or can be executed by the dedicated hardware such as a DSP circuit (chip100 in FIG. 3) assigned to this task. As used herein, the terms circuitand program are both used to describe the architecture for carrying outthe steps illustrated in FIGS. 6 and 7.

[0058] The specific improvements of the invention are illustrated byreference to FIGS. 6-10. At the beginning of the test, shown at 201 ofFIG. 6, the QT interval is detected. Each successive QT interval duringalternans train detecting is passed through a high pass filter as shownat 202, in order to remove low frequency components to the QT signal.Thus, the high pass filter effectively removes the average value of QTand provides at its output a QT interval change, either plus or minusaround the average value. This is illustrated in the bottom curve ofFIG. 8, which shows a plot of typical QT values after having passedthrough the high pass filter. Each filtered QT interval signal is passedinto a delay queue, comprising n−1 delay elements 204,206 - - - 208. Thenomenclature Z−1 indicates a delay of one sample interval cycle, i.e., adelay of one R-R interval. Each just detected filtered QT intervalsignal is connected to a multiplier element 210-1, shown as f1, whileeach previous sample is connected to a queue position related multiplierelement (210-2 . . . 210-n). As seen in FIG. 6, f1 . . . fn are themultiplier factors, and may be for example, 1, minus 1, 1, minus 1, . .. . Thus for the current transformation, the just detected QT intervalis multiplied by f1; the previous sample by f2; and the last sample inthe queue by fn−1. For each transformation operation the outputs of themultiplier elements f1-fn are added by adder elements 220, 221 . . .222, to provide a transformation output. This output, which may besigned plus or minus, is processed through absolute element 224, whichsuitably squares the sum of the total to provide an output having anabsolute value. This in turn is inputted to a comparator 225, andcompared to a noise threshold signal to determine whether or not thereis TWA. The result of the comparison is handled at block 250, and givesan output when there is TWA.

[0059]FIG. 8 shows a representative match in the upper graph,corresponding to the filtered QT interval data shown in the bottomgraph. Examination of the QT interval graph shows that high passvariations from beat to beat are relatively small, and in this exampleare between plus and minus two ms. In any given case, variations may belarger, but could be within only several ms. Given this knowledge, it isimportant to take into account the noise level on the V-sense channel,in order to determine whether the alternans match is a validrepresentation of TWA or is in fact a product primarily of noise. Forthis reason a noise threshold signal is developed as seen in the lowerbranch of FIG. 6. At 228 a maximum noise level, e.g., 0-2 ms ininputted, and at 229 a minimum noise level in the same range isinputted. These are default values that are pre-determined based onsample accuracy and normal variations. In the illustration of FIG. 8 theswings of QT interval data (representing different values from beat tobeat, after the high pass filtering) are seen to be in the range ofabout 0.5 to 2.0. For this example, the maximum noise value may be set,e.g., at 1.0 ms. and the minimum noise value may be set, e.g., at −1.0ms. The max and min noise values are operated on by the respectively oddand even elements in an array of n multiplier factors, shown at 230-1through 230-n. The multiplied values are summed at adding elements shownat 240, 241 . . . 242, and then made absolute as shown at element 245.The operation at elements 224 and 245 are the same and suitably maysimply involve squaring the summation values presented to each. Theoutput from 245 is inputted to comparator 225 as a noise thresholdvalue. In one embodiment of the invention, if the output of theoperation at 224 exceeds the threshold value from 245, a signal ispassed to TWA analysis element 250, where TWA is declared. It is to beunderstood that other steps may be added to the determination of TWA.For example, TWA can be declared only after the alternans match fromelement 225 exceeds the noise threshold from 245 for x consecutivecycles, or for some fraction of cycles. Further, a constant can be addedto the output of element 245, to ensure that the alternans match issufficiently above noise to guarantee declaration of TWA.

[0060] Inspection of FIG. 8 shows the operation by which alternans matchvalues, generated by the step shown at 224, relate to QT interval data.As is seen, the high pass filtered QT interval data varies above andbelow the zero reference line, representing an alternating QT interval.The match graph represents data taken from a one, minus one, one array(also represented as [1,−1,1] with the match value corresponding to thecenter QT measurement. In this actual example of patient data, the noisedetection threshold is ten, and the alternans is spotted above thislevel as indicated at the circled dots. Each match figure corresponds tothe center QT interval, i.e., the match represents the transformationobtained by operating on the current QT interval, the prior QT intervaland the next following QT interval. For example, the first match that iscircled indicates an alternans match having a value of about 12.25. Thiswas obtained by operating on QT values of minus 1.2, plus 1.4, and minus0.9. When these values were multiplied and summed by the array [1,−1, 1]this yields 3.5. The value of 3.5 squared equals 12.25.

[0061] As illustrated in FIG. 6, high pass filtering is done prior tothe transformation. Further advantage can be obtained by eliminating thefiltering as a separate step and incorporating it into thetransformation, which makes the implementation easier and reduces thecomputer or processor requirements. A high pass filtering function isobtained by operating on the array for the previous sample by minus 1and the array for the current sample by plus 1. Adding these twooperations together, an array, or template [−1,+2,−1] is changed to[−1,3,−3,1]. Thus, an n factor array for use with the high pass filteredsignal is replaced by an n+1 array for an unfiltered signal. The changedarray accentuates the differences from beat to beat so as to provide thehigh pass filter function. Thus, instead of the operation shown if FIG.6 of first high pass filtering the QT interval, the high pass filteroperation shown at 202 is eliminated and the n array is changed toincorporate the high pass filtering function. In the latter case, allthe inputted QT values are of the same sign and accordingly for an arrayor template having an odd number of factors, the A-B-A-B-A pattern ischanged to the following: 1, 1+1/n, −1, 1+1/n, −1 . . .

[0062] The transformation array of FIG. 6 can be embodied by hardware orsoftware. Implementation in either form is within the ordinary skill ofone in the art area. A hardware embodiment suitably incorporates a DSPchip under command of the microprocessor. The delay functions areaccomplished by cyclically clocking each value of QT to a next locationin a software queue, following which the multiplication and additionfunctions are carried out.

[0063] A software embodiment of the array transformation is illustratedin FIG. 7. At the start of a new test the queue is erased, as shown at260. At 261 the device waits for the next QT, and at 262 a new QT isreceived. At 264 a factor k is set to n−1, where n is the number offactors in the array. At 265 QTk+1=QTk, meaning that the kth value of QTis advanced to the next position, corresponding to a delay functionillustrated in FIG. 6 by a “Z−1” element. Next, at 266, k is set=k−1. At267 a check is made to see if k=0, which would mean that all previouslystored QT values have been advanced in the queue. If not, the programsloops back to 265 and repeats until k=0. When all the previously storedQT values are advanced, at 263 the new QT is designated QT1. At thattime, the program checks to see that there is indeed a value for QTn,meaning the queue is full. If not, as happens when a test first startsand it takes n cycles to fill the queue, the program returns to 261 andwaits for the next QT. When a value of QTn is found at 268, the queue isready and the program proceeds to carry out the multiplication andaddition functions as shown at 272, 274, 275 and 276. When these havebeen completed, as determined at 275, the array transformation iscomplete and the QT alternans value QTalt is obtained. The program thengoes on to the step of making QTalt absolute, and comparing with thenoise threshold. The steps for generating the noise threshold arestraightforward multiplication and addition steps, as illustrated inFIG. 6. Of course, the noise threshold need be calculated only once foreach test; but whenever the array is changed, i.e., n is changed, thenthe noise threshold must again be calculated.

[0064] As noted above, the terms “program” and “circuit” are used in theclaims to denote either a hardware or software embodiment. Thus, acircuit or circuitry can be, e.g., DSP circuitry or a programmedmicroprocessor system.

[0065]FIG. 9 represents a flow diagram showing the primary functions ofa complete alternans test. The start of the test is indicated at 300 andmay either be initiated from an external source by sending a programmersignal, or may be initiated automatically by an internal timer in theimplanted device. Two paths are undertaken concurrently, at 302 and 310.At 302, the patient initiates exercise and the device waits for atrigger indicating that the heartbeat has been raised to an appropriatelevel. Alternately, the device may go into an overdrive-pacing mode andraise the patient heart rate appropriately. At 304, QT or another T-waveindicator is measured, each successive QT interval value being inputtedto the array for transformation as indicated at 306, using previouslyrecorded QT intervals. The array, or pattern is set by an input from TWApattern memory 307, which is suitably programmable as discussed furtherin the connection with FIG. 10. Note that step 306 includes the highpass filter function, either by separate hardware or as part of thetransformation. Each cycle the array transformation is performed at 306,and at 308 the resulting value is made absolute. At the same time, theminimal and the maximal noise thresholds are obtained at 310,transformed at 312 and made absolute at 314. The noise threshold valueis inputted to the compare block 320 along with the array output, andcompared. At 322 it is determined whether there is TWA. If yes, a pacingparameter, e.g. the upper pacing rate, is suitably changed as indicatedat 324. Whether there is TWA or not, the result of the test is stored at326.

[0066]FIG. 10 is a flow diagram showing an embodiment of the inventionwhere multiple tests may be taken and the transformation array may bechanged, either in a programmed manner or as a function of past results.The test is started at 400, and at 401 pacing rate is elevated asnecessary. At 404 the array is set in accord with how the test has beenprogrammed. In one embodiment, the array is set to a default array,which may be the last array that had been used. However, the array to beused may be programmable, and selected from arrays having different “f”and different values of n. Also, at this time an indicator may be setfor later use, for indicating that at least a second test is to beperformed using a second array. After n cycles, the array transformationis performed at 406 and at 408 a determination is made whether there isTWA. If no, at 409 the program determines whether another test with adifferent array is to be determined. This programmable feature ispresented because the test may be array dependent, and it can beimportant to determine the types of arrays that detect TWA and thosethat are relatively inefficient. If yes, the new array is loaded and theprogram returns to 406 to do another transformation. If no, the TWAnegative result is updated in a histogram as indicated at 422, and at424 the routine is exited and the device returns to normal pacing. Thehistogram storage may be a histogram of alternans match levels, or ofTWA/no TWA for each array. If there is TWA, this result is stored intemporary memory as indicated at 410. At 415 it is determined whetherthe device is programmed to repeat the task and look for successivealternans indications. If no, the test data is stored at 417, and at 419pacing may be changed and an alert can be set. However, if at 415 thedecision is to repeat the task, at 418 it is determined whether thearray, or template is to be changed. This step may programmedautomatically, and may suitably involve examination of the histogramdata. If yes, it is changed at 420 and the routine moves back to 406 tocontinue array transformation based on the changed array. In thismanner, a series of tests can be made, with the result of each beingstored. After the series is ended, the temporarily stored data isutilized at 422 to update the histogram storage, indicating the resultsof the alternans tests with different arrays. This histogram data can beused subsequently to reprogram the arrays used, and for diagnosticpurposes.

[0067] In an embodiment of this invention, a plurality of arrays arestored in the implanted device, for use as selected. The value of n forthe arrays may be programmably selected, or automatically selected, toprovide the optimum amount of flexibility and capability of determiningwhat array or arrays work best for the patient. The arrays arepreferably stored in software and the transformation is carried out bythe microporcessor. However, the array memory and operation may beembodied as hardware, e.g., DSP or other equivalent digital hardwareprocessing circuitry.

[0068] From the above, it is seen that an improved method and means of“spotting” or detecting alternans is provided. By high pass filteringand operating on differential changes each cycle, alternans isefficiently detected as soon as it exists in the patient. Further, byprogramming the array and keeping track of the results of alternanstests with different arrays, the most effective test for the individualpatient can be determined and used.

[0069] Some of the techniques described above may be embodied as acomputer-readable medium comprising instructions for a programmableprocessor such as microprocessor 51 or pacer timing/control circuitry 63shown in FIG. 5, for example. The programmable processor may include oneor more individual processors, which may act independently or inconcert. A “computer-readable medium” includes but is not limited to anytype of computer memory such as floppy disks, conventional hard disks,CR-ROMS, Flash ROMS, nonvolatile ROMS, RAM and a magnetic or opticalstorage medium. The medium may include instructions for causing aprocessor to perform any of the features described above for initiatinga session of the escape rate variation according to the presentinvention.

[0070] The preceding specific embodiments are illustrative of thepractice of the invention. It is to be understood, therefore, that otherexpedients known to those skilled in the art or disclosed herein, may beemployed without departing from the invention or the scope of theappended claims. The present invention is not limited to any particularcombination of hardware and software per se, but may find applicationwith any form of software supplementing hardware.

[0071] In the claims, means-plus-function clauses are intended to coverthe structures described herein as performing the recited function andnot only structural equivalents but also equivalent structures. Thus,although a nail and a screw may not be structural equivalents in that anail employs a cylindrical surface to secure wooden parts together,whereas a screw employs a helical surface, in the environment offastening wooden parts a nail and a screw are equivalent structures.Likewise, an implantable medical device that has elements thatincorporate presently unforeseeable technology but perform the samefunctions within the context of the device are within the scope of theinvention.

What is claimed is:
 1. An implantable medical device comprising: a ventricular sensor operative to sense ventricular signals; a sensor operative to obtain a measure of QT interval for each sensed ventricular signal; criteria circuitry for producing at least one criterion value relevant to T-wave alternans detection; a transformation program adapted to process each QT measure in accord with a predetermined transformation array to produce an alternans match; and an alternans identifying program that identifies T-wave alternans in response to said alternans match meeting said at least one criterion value.
 2. The device of claim 1, wherein said criteria circuitry comprises a noise adjustment circuit that provides a noise signal representative of the noise component of said each sensed ventricular signal.
 3. The device of claim 2, wherein said program comprises comparing means operative each cardiac cycle for comparing each alternans match with a measure of said noise signal.
 4. The device of claim 1, comprising a high pass filter operatively acting on said QT measure before processing in said transformation program.
 5. The device of claim 4, wherein said high pass filter is a hardware filter.
 6. The device of claim 4, wherein said high pass filter comprises DSP circuitry.
 7. The device of claim 1, wherein said transformation program comprises a high pass filter function.
 8. The device of claim 1, wherein said transformation program comprises a pattern array of n multiplier factors.
 9. The device of claim 8, wherein said program comprises multipliers for multiplying each of said n factors times a respective one of a series of n consecutive QT interval measures.
 10. The device of claim 8, comprising a selection circuit for selecting n.
 11. The device of claim 8, comprising a factor circuit for setting each of said n factors.
 12. The device of claim 9, wherein said transformation program comprises adders for obtaining a summation of said multiplications.
 13. The device of claim 8, comprising a programmer for programming the value of each of said factors.
 14. The device of claim 9, wherein said array comprises multiplier factors of alternating signs, wherein successive measures of QT are multiplied by factors of alternating signs.
 15. The device of claim 1, comprising an absolute circuit that makes the alternans match an absolute value.
 16. The device of claim 2, wherein the noise adjustment circuit comprises maximum and minimum noise sources, and a transformation circuit with a n factor alternating sign array for producing a noise threshold signal.
 17. The device of claim 16, comprising a comparator circuit for comparing said alternans match with said noise threshold signal to detect the presence or absence of T-wave alternans.
 18. The device of claim 17, comprising a change circuit for changing at least on pacing parameter in response to detected T-wave alternans.
 19. The device of claim 17, comprising storage circuitry for storing data relating to detected T-wave alternans.
 20. An implantable medical device system, comprising: means for cyclically for obtaining a measure of a QRS-T wave; means for cyclically operating on the last n consecutive said measures with an alternating transformation to obtain an alternans match; and means for determining when said match indicates the presence of T-wave alternans.
 21. The system of claim 20, wherein said means for cyclically obtaining comprises T-wave means for determining the QT interval each cycle of operation as said measure.
 22. The system of claim 21, wherein said means for cyclically operating comprises a pattern of alternating sign multiplication factors, means for queuing the last n said QT intervals, means for multiplying each said queued QT interval by a said factor corresponding to the position of the QT interval in the queue, and means for summing the n values obtained by said multiplying.
 23. The system of claim 22, wherein said pattern comprises n alternating sign unit factors (1, −1, 1, −1, . . . ).
 24. The system of claim 22, wherein said pattern comprises factors that are adjusted to provide a high pass filter operation.
 25. The system of claim 20, comprising high pass filter means for filtering out low frequency changes in said measures.
 26. The system of claim 25, wherein said high pass filter means comprises a digital filter.
 27. The system of claim 25, wherein said means for cyclically operating comprises said high pass filter means.
 28. The system of claim 20, further comprising means for cyclically generating a noise threshold signal representative of the noise level in each respective alternans signal, and means for comparing each consecutive alternans match to the respective noise threshold signal generated for the same cycle to determine if there is T-wave alternans.
 29. The system of claim 28, wherein said means for cyclically operating further comprises means for converting the alternans match and the threshold signal to absolute values.
 30. The system of claim 20, wherein said means for cyclically operating comprises a pattern of n alternating sign factors, where n is between 3 and 10, and said means for cyclically operating operates on n consecutive said measures in accord with said pattern.
 31. The system of claim 20, further comprising means for initiating operation of said means for cyclically obtaining, said means for cyclically operating and said T-wave alternans means so as to provide determinations of T-wave alternans on a consecutive cycle basis.
 32. The system of claim 20, wherein said means for cyclically operating comprises a software program.
 33. A method of determining an indication of T-wave alternans in a patient, comprising: cyclically obtaining QT interval values; developing a queue of n values representative of consecutive QT interval values; transforming said n values with a predetermined transformation array to obtain a T-wave alternans match; and comparing said T-wave alternans match to at least one T-wave alternans threshold value to provide said indication of T-wave alternans.
 34. The method of claim 33, comprising using an implantable medical device and storing at least one said array in said device.
 35. The method of claim 33, comprising storing a plurality of arrays in said device, and programmably selecting at least one of said arrays for use in said transforming step.
 36. The method of claim 33, comprising providing a plurality of transformation arrays, and carrying out said transformation step with at least two respective said arrays.
 37. The method of claim 33, comprising determining a noise threshold value for comparing with said match.
 38. The method of claim 36, comprising cyclically maximum and minimum noise threshold signals and determining said noise threshold value from said maximum and minimum signals.
 39. The method of claim 33, comprising high pass filtering said QT values to obtain said representative signals.
 40. The method of claim 33, comprising providing at least one transformation array that includes high pass filtering of the QT values, and high pass filtering concurrently with transforming
 41. A method of determining an indication of alternans in an implanted medical device, comprising: cyclically obtaining measures of QT intervals; high pass filtering the measures to substantially remove predetermined components associated with a predetermined change from cycle to cycle; processing said filtered measures cyclically by wave transformation, and obtaining from said transformation a measure of alternans match; determining when said measure of alternans match indicates alternans.
 42. The method of claim 41, further comprising using a cardiac pacemaker as said medical device, and changing at least one pacing parameter of said pacemaker in response to an indication of alternans.
 43. The method of claim 42, further comprising storing at least one transformation array in said pacemaker, and using said array in said processing step.
 44. The method of claim 42, further comprising providing memory for a plurality of transformation arrays in said pacemaker, and programming respective arrays into said memory.
 45. The method of claim 42, wherein said determining step comprises comparing said measure of alternans match to a predetermined alternans threshold.
 46. The method of claim 45, further comprising generating a noise threshold signal and using said signal as said alternans threshold.
 47. The method of claim 43, further comprising an array having n multipliers, and selecting n as a number between 3 and
 10. 48. The method of claim 47, further comprising an array with multiplier factors that provide for high pass filtering of the measures.
 49. The measure of claim 47, further comprising making the alternans match an absolute value.
 50. An implantable medical system, comprising: a circuit for cyclically detecting QT intervals; a transform array program containing elements providing for operating on n of said QT intervals; a control circuit operating cyclically to carry out the operations of said array and to produce a value indicative of the degree of T-wave alternans; and a threshold circuit operating on said indicative value and detecting T-wave alternans as a function of said value.
 51. The system of claim 50, wherein said control circuit operates cyclically to form a queue of the n most recent QT intervals.
 52. The system of claim 51, wherein said transform array program comprises n alternating sign multipliers, wherein said n QT intervals are multiplied by alternating signs.
 53. The system of claim 52, wherein said transform array program comprises adders for obtaining a summation of the said multiplier products.
 54. The system of claim 53, further comprising an absolute circuit for converting said summation to an absolute value.
 55. The system of claim 54, further comprising a comparator, wherein said threshold circuit provides a noise threshold signal indicative of the absolute value of noise that accompanies said QT intervals, and said comparator compares said noise value and said summation absolute value.
 56. The system of claim 55, further comprising a high pass filter for high pass filtering said QT intervals.
 57. The system of claim 56, wherein said elements of said transform array program comprise elements that provide high pass filtering of the QT intervals.
 58. A computer readable medium having computer executable instructions for performing a method comprising: cyclically obtaining values of QT intervals; developing a queue of n values representative of consecutive QT interval values; transforming said n values with a predetermined transformation array to obtain a T-wave alternans match; and comparing said match to at least one T-wave alternans threshold value to provide an indication of T-wave alternans. 